[Show abstract][Hide abstract]ABSTRACT: Liver transplantation improves survival of patients with end-stage (Child-Pugh stage C) alcoholic cirrhosis, but its benefit for patients with stage B disease is uncertain.
To compare the outcomes of patients with Child-Pugh stage B alcoholic cirrhosis who are immediately listed for liver transplantation with those of patients assigned to standard treatment with delay of transplantation until progression to stage C disease.
Randomized, controlled trial.
13 liver transplantation programs in France.
120 patients with Child-Pugh stage B alcoholic cirrhosis and no viral hepatitis, cancer, or contraindication to transplantation.
Patients were randomly assigned to immediate listing for liver transplantation (60 patients) or standard care (60 patients).
Overall and cancer-free survival over 5 years.
Sixty-eight percent of patients assigned to immediate listing for liver transplantation and 25% of those assigned to standard care received a liver transplant. All-cause death and cirrhosis-related death did not statistically differ between the 2 groups: 5-year survival was 58% (95% CI, 43% to 70%) for those assigned to immediate listing versus 69% (CI, 54% to 80%) for those assigned to standard care. In multivariate analysis, independent predictors of long-term survival were absence of ongoing alcohol consumption (hazard ratio, 7.604 [CI, 2.395 to 24.154]), recovery from Child-Pugh stage C (hazard ratio, 7.633 [CI, 2.392 to 24.390]), and baseline Child-Pugh score less than 8 (hazard ratio, 2.664 [CI, 1.052 to 6.746]). Immediate listing for transplantation was associated with an increased risk for extrahepatic cancer: The 5-year cancer-free survival rate was 63% (CI, 43% to 77%) for patients who were immediately listed and 94% (CI, 81% to 98%) for those who received standard care.
Restriction of the study sample to alcoholic patients may limit the generalizability of results to other settings.
Immediate listing for liver transplantation did not show a survival benefit compared with standard care for Child-Pugh stage B alcoholic cirrhosis. In addition, immediate listing for transplantation increased the risk for extrahepatic cancer.
The French National Program for Clinical Research.

[Show abstract][Hide abstract]ABSTRACT: Acute rejection is still a common complication of hepatic transplantation. The diagnosis, based on the histological examination of the graft, may be difficult to confirm in the setting of combined hepatitis C virus infection. The presence of C4d in the portal capillaries could facilitate differentiation between acute rejection and relapsed hepatitis C. The deposit of C4d provides evidence of activation of humoral immunity. To attempt to confirm this hypothesis, we searched for the presence of C4d in posttransplant hepatic biopsies.
Thirty-six biopsies from 34 patients were analyzed retrospectively. The samples had been requested for one of the following reasons: suspected rejection, relapsed hepatitis C infection, or systematic check-up 1 year after the transplant.
C4d expression was common in biopsies classified as acute rejection (33%) and chronic rejection (100%). C4d was never detected in the event of recurrent hepatitis C infection without rejection.
These results, which are comparable to recently published data, give credence to the theory that C4d could be used as a marker for rejection following hepatic transplantation.

[Show abstract][Hide abstract]ABSTRACT: Hepatocellular carcinoma (HCC) is the most frequent primitive cancer of the liver. It mostly develops on cirrhotic livers. Orthotopic liver transplantation is the only treatment that definitively addresses both the metachronous occurrence risk of HCC and the underlying disease. Under Milan criteria, i.e. less than 3 nodules of 3 cm max in diameter, or 1 nodule of 5 cm maximum, OLT has been shown effective and provides with survival rates almost equal to those obtained with HCC free cirrhotic patients. In Rennes, 195 patients with early HCC on cirrhotic livers have been transplanted from January 1995 to June 2005. Global and disease free 8 years patient survival rates were 73 and 70%, respectively. These results were significantly altered when the recipient was female, the cirrhosis due to C virus and the patient of B blood group. Despite these excellent results, the principal limit to the application of transplantation for HCC remains the long period of time patients have to wait for a graft. During this period of time, growth of the tumour may drop the patient out of Milan criteria and subsequently from the waiting list. The role of chemoembolisation, liver resection and thermal ablation while the patient is waiting for a graft remains debatable.

[Show abstract][Hide abstract]ABSTRACT: Potential antiviral properties of cyclosporine against hepatitis C virus have been highlighted in several publications. Therefore, we investigated the effect of a switch from tacrolimus to cyclosporine in a liver transplant recipient with recurrent hepatitis C who did not respond to antiviral therapy. The patient received a liver transplant for hepatitis C cirrhosis. Initial immunosuppressive treatment was based on tacrolimus. Because of viral activity, a combined therapy was initiated 20 months later including interferon and ribavirine. Then, due to a lack of virological and biochemical response, tacrolimus was replaced by cyclosporine (Neoral), while maintaining the same antiviral therapy. Decreases in the viral load and transaminases levels were observed.

[Show abstract][Hide abstract]ABSTRACT: The objective of this prospective study was to determine whether sociological and/or alcohol-related behavioral factors could be predictive of relapse after orthotopic liver transplantation for alcoholic liver disease.
Fifty-five liver-transplanted patients out of a series of 120 alcoholic cirrhotic patients were enrolled in a randomized prospective study. This study was initially designed to compare the 2 year survival in intent-to-transplant patients versus in-intent-to-use conventional treatment patients. For all patients, an identical questionnaire was completed at inclusion, and every 3 months for 5 years to collect data on alcohol-related behavior factors.
Fifty-one patients fulfilled the criteria for the study. The mean follow-up was 35.7 months (range: 1-86). Rate of alcohol relapse was 11% at one year and 30% at 2 years. Alcohol intake above 140 g a week was declared by 11% and 22% of patients at one and 2 years, respectively. The only variable leading to a significantly lower rate of relapse was abstinence for 6 months or more before liver transplantation (23% vs 79%, P=0.0003). This variable was also significant for patients whose alcohol intake was greater than 140 g per week (P=0.003) (adjusted relative risk=5.5; 95%CI=1.3-24.5; P=0.02). Multivariate analysis (Cox model) showed that abstinence for 6 months or more before liver transplantation was the unique predictive variable.
In this prospective study of 51 patients transplanted for alcoholic liver disease, abstinence before liver transplantation was the only predictive factor of alcohol relapse after liver transplantation.

[Show abstract][Hide abstract]ABSTRACT: Recurrence is common after surgery for hepatocellular carcinoma (HCC).
The efficacy of, and tolerance to, preoperative intra-arterial injection of (131)I-labelled lipiodol was examined in 34 patients with HCC, including 29 with cirrhosis. Twenty-five patients had a single hepatic tumour and the mean(s.d.) tumour size was 5.2(3.7) (range 2-15) cm. The patients received between one and three injections of (131)I-labelled lipiodol (60 mCi per injection) before surgery. Operations included 14 liver transplants, 13 minor hepatectomies, six major hepatectomies and one exploratory laparotomy.
There was one complication after lipiodol injection due to acute ischaemia of the small bowel. Three of 34 patients died within 28 days, two after transplantation and one after resection. An objective tumour response (decrease in tumour size) was observed in 19 of 34 patients, and a complete histological response in eight of 34. There was an objective tumour response or major histological necrosis of lesions in 25 of 34 patients. The 5-year survival rate was 48.4(8.0) per cent, 69.0 per cent after transplantation and 36.0 per cent in patients who underwent resection.
This preoperative method appeared to be well tolerated, and provided promising results in terms of macroscopic and microscopic tumour responses.

[Show abstract][Hide abstract]ABSTRACT: Recurrence is common after surgery for hepatocellular carcinoma (HCC).
The efficacy of, and tolerance to, preoperative intra-arterial injection of (131)I-labelled lipiodol was examined in 34 patients with HCC, including 29 with cirrhosis. Twenty-five patients had a single hepatic tumour and the mean(s.d.) tumour size was 5.2(3.7) (range 2-15) cm. The patients received between one and three injections of (131)I-labelled lipiodol (60 mCi per injection) before surgery. Operations included 14 liver transplants, 13 minor hepatectomies, six major hepatectomies and one exploratory laparotomy.
There was one complication after lipiodol injection due to acute ischaemia of the small bowel. Three of 34 patients died within 28 days, two after transplantation and one after resection. An objective tumour response (decrease in tumour size) was observed in 19 of 34 patients, and a complete histological response in eight of 34. There was an objective tumour response or major histological necrosis of lesions in 25 of 34 patients. The 5-year survival rate was 48.4(8.0) per cent, 69.0 per cent after transplantation and 36.0 per cent in patients who underwent resection.
This preoperative method appeared to be well tolerated, and provided promising results in terms of macroscopic and microscopic tumour responses.

[Show abstract][Hide abstract]ABSTRACT: A single dose of recombinant factor VIIa (rFVIIa) has been shown to be effective and safe in correcting the prothrombin time (PT) in cirrhotic patients, but no clinical data exists demonstrating its efficacy in arresting active bleeding.
rFVIIa was used in two cirrhotic patients for persistent bleeding following dental extractions despite repeated treatment at the wound site and, in one case, repeated administrations of fresh-frozen plasma (FFP).
Bleeding stopped promptly in both patients after administration of rFVIIa. However, bleeding recurred in the patient who had not received concomitant treatment at the extraction sites. No recurrence of bleeding was observed in the second patient, who underwent local treatment 15 min after rFVIIa.
Recombinant factor VIIa arrested bleeding after dental extractions in two cirrhotic patients who had been unsuccessfully treated with FFP. However, additional local treatment is needed to limit the risk of recurrence as a result of the short half-life of rFVIIa.

[Show abstract][Hide abstract]ABSTRACT: The aim of our study was to evaluate the proportion of patients with severe alcoholic cirrhosis who would need orthotopic liver transplantation (OLT) and to determine the optimal delay to evaluate an abstinent patient for transplantation.
Survival without OLT, improvement in liver function and need for OLT were studied in all patients admitted in 1997 for a first episode of Child-Pugh C alcoholic cirrhosis.
Twenty-six percent (19/74) of patients died during the initial hospitalization. The cumulative survival rates after 6 months and 1, 2 and 3 years were 56, 36, 35 and 24%, respectively. One liver transplantation (1.3%, 95% confidence interval 0.0-3.9) was performed for persisting liver failure despite abstinence. Improvement of the Child-Pugh score was observed within 3 months in 66% of the abstinent patients. OLT was indicated in four patients without liver improvement despite abstinence, but was contraindicated in three.
Only a few patients with severe alcoholic cirrhosis undergo OLT, since most of them do not stop drinking and/or die soon, and those becoming abstinent often improve their liver function. OLT should be considered when improvement in liver function is lacking after 3 months of abstinence.

[Show abstract][Hide abstract]ABSTRACT: We studied the outcome of 345 liver transplant patients who received tacrolimus-based immunosuppressive therapy either as a dual regimen (with corticosteroids, n=172) or as a triple regimen (with corticosteroids and azathioprine, n=173) for 3 months after transplantation (3-month cohort). A further analysis was conducted for the first 195 patients randomised (dual n=100, triple n=95) who were followed up for 12 months after transplantation (12-month cohort). For the 3-month cohort, patient survival was 90.7% (dual) and 91.9% (triple), graft survival after 3 months was 88.4% (dual therapy) and 89.6% (triple therapy). Acute rejections were experienced by 67/172, 39.0% of patients on dual therapy and by 60/173, 34.7% of patients on triple therapy; corticosteroid-resistant rejections were reported in 9 patients (5.2%) in either treatment group. The overall safety profile was similar for the two treatment groups. Significant differences, however, were found for thrombocytopenia (dual 13/172, 7.6%, triple 37/173, 21.4%, p<0.001) and leukopenia (dual 4/172, 2.3%, triple 24/173, 13.9%, p<0.001). For the 12-month cohort, patient survival was 85.6% (dual) and 88.4% (triple) after 1 year. Graft survival was 81.7% (dual) and 85.2% (triple) 12 months after transplantation. Acute rejections were reported for 38/100, 38.0% of patients on dual therapy and 36/95, 37.9% of patients on triple therapy, corticosteroid-resistant rejections were 7/100, 7.0% (dual) and 7/95, 7.4% (triple) of patients. In the 12-month cohort, no significant differences in the safety profiles of the treatment groups were found. We conclude that both tacrolimus-based dual and triple drug regimens provide effective and safe immunosuppression following orthotopic liver transplantation.

[Show abstract][Hide abstract]ABSTRACT: This prospective randomized trial was carried out in order to determine whether the long-term administration of ursodeoxycholic acid after discontinuation of interferon had any beneficial effect on the clinical course of hepatitis C virus infection.
Enrolled in the study were 203 patients with chronic active hepatitis C. They were all given: interferon alpha-2a (3 MU subcutaneously thrice a week) and ursodeoxycholic acid (10 mg/kg/day) for 9 months. At month 9, biochemical responders only were randomized into ursodeoxycholic acid treatment or placebo for 12 additional months (double blind study).
At the end of interferon therapy, 71 patients (37%) were virological responders and 107 (56%) patients were biochemical responders and were randomized: 54 into the ursodeoxycholic acid group and 53 into the placebo group. Sustained response was evaluated 12 months after withdrawal of interferon. Sustained biochemical and virological responses were, respectively, 30% and 22% in the ursodeoxycholic acid group and 46% and 32% in the placebo group, which did not significantly differ. Histological evolution of fibrosis and necrotic inflammatory activity were similar in the two groups.
Continuation of ursodeoxycholic acid therapy after withdrawal of interferon in patients with end-of-treatment response did not result in any significant improvement either in the maintenance of response to interferon or in liver histology.

[Show abstract][Hide abstract]ABSTRACT: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for "prioritisation", favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis.
We compared the survival of 169 transplanted patients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients.
The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58-74%) vs. 52% (44-60; p = 0.03) in the matched group and 54% (51-57; p = 0.01) in the simulated controls. Transplantation was associated with survival (relative risk = 1.51; p = 0.02), independently of risk score (risk = 2.07; p<0.001), indication, period of inclusion, centre experience, and alcohol abstinence. Patients with severe disease (Pugh C11-15) benefited most in terms of 5-year survival: 58% (44-72) vs. 31% (17-45; p = 0.008) in the matched and 35% (30-40; p<0.001) in the simulated control groups. For patients at lower risk there was no significant difference.
Liver transplantation increases the 5-year survival of patients with severe alcoholic cirrhosis. In patients at lower risk, efficacy of transplantation should be confirmed by longer follow-up or by randomised trial.

[Show abstract][Hide abstract]ABSTRACT: Background/Aims: Alcoholic cirrhosis is the most common cause of liver transplantation in US males. The limited number of donor livers calls for“prioritisation”, favouring those patients who will benefit most. The aim was to assess the efficacy of liver transplantation in patients with alcoholic cirrhosis.Methods: We compared the survival of 169 transplantedpatients with two conservatively treated control groups, one of 169 patients matched for prognostic factors (age, cirrhosis severity, bleeding history) and one of 169 simulated patients.Results: The probability of survival to 5 years in the transplanted group was 66% (95% confidence interval 58–74%) vs 52% (44–60; p=0.03) in the matched group and 54% (51–57; p=0.01) in the simulated controls. Transplantation was associated with survival (relative risk=1.51; p=0.02), independently of risk score (risk=2.07; p

[Show abstract][Hide abstract]ABSTRACT: HBV reinfection of transplant livers occurs frequently even in the presence of high doses of anti-HBs immunoglobulins. We analyzed, retrospectively, whether and which type of S-gene variants were selected by long-term polyclonal anti-HBs (HBIg) treatment leading to reinfection of patients transplanted because of chronic HBs-positive end-stage liver disease.
The preS2/S gene of the viral genomes obtained from sera before transplantation and during HBV reinfection was amplified by PCR and directly sequenced.
According to transaminase and HBV DNA hybridization analysis, 3/18 (17%) liver transplant patients had HBV and hepatitis recurrence during anti-HBs therapy. A HBV S-gene mutant containing a G to A nucleotide mutation at position 587, converting Glycine to Arginine (G145A), was identified in all three patients as the dominant population at reinfection but not pre-transplantation. Contrary to the S-gene, no consistent nucleotide changes were found in the pre-S2 region of HBV genomes when comparing the reinfection and pre-transplantation samples.
These data demonstrate that long-term polyclonal anti-HBs immunoprophylaxis selected the most commonly described G145R S-gene escape HBV variant which became the dominant virus population and was responsible for graft infection. Therefore, immunoglobulins with high affinity for the G145R HBs variant should be included in HBIg to prevent recurrent HBV infection in transplant patients.